Glioblastoma cells grown in the lab. Credit: Dr Susan Short
Targeting a molecule that helps cells repair their DNA could lead to a new treatment for some aggressive brain tumours, a University of Leeds study has found.
Researchers discovered that switching off the RAD51 molecule increased the effectiveness of radiotherapy to kill glioblastoma cells in the lab.
Glioblastomas are the most common type of brain tumour in adults. They are also the hardest to treat, with fewer than 5 in every 100 people surviving their disease for at least 5 years after diagnosis.
The study, funded by Cancer Research UK, was published in the journal Stem Cell Reports.
“By targeting RAD51 with an inhibitor we were able to make these GSCs more sensitive to the effects of radiotherapy, helping remove the tumour.” – Dr Susan Short, lead author
Dr Justine Alford, Cancer Research UK’s senior science information officer, said that new, kinder treatments for glioblastoma were urgently needed.
“This promising study in cells and mice may have found a way to cut off the tumour’s fuel supply,” she added.
If the approach proves safe and effective in larger studies with people, it “could one day help treatments target the disease more precisely and effectively”, said Alford.
Researchers had suggested that some specialised groups of glioblastoma cells can reproduce to make identical copies that are more resistant to treatment.
And the Leeds researchers found that this subgroup, called glioblastoma stem cells (GSCs), have high levels of the RAD51 molecule.
RAD51 helps cancer cells repair the damage that radiotherapy causes to their DNA, said Professor Susan Short, lead author of the study.
This repair allows the cancer cells to bounce back after treatment and repopulate the tumour. But working with mice, the team were able to reverse these effects using an experimental drug – or inhibitor – that targets RAD51.
“By targeting RAD51 with an inhibitor we were able to make these GSCs more sensitive to the effects of radiotherapy, helping remove the tumour,” said Short.
“The exact mechanism by which RAD51 becomes increased in cells that survive radiotherapy is not yet known, but our study provides strong evidence that this is the right protein to target in the treatment of this aggressive brain cancer.”
The experimental drugs used in this study are not yet suitable for clinical trials, so the next step will be to develop a similar drug that has the same effects in the lab and can be safely tested in people.
Short, S. et al (2017) RAD51 is a Selective DNA Repair Target to Radiosensitise Glioma Stem Cells. Stem Cell Reports.